Home LiteratureArticle Details
PMID: 15170261 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Abundance, distribution, and mutation rates of homopolymeric nucleotide runs in the genome of Caenorhabditis elegans.

Journal of molecular evolution ·Vol. 58 ·No. 5 ·2004-05-00 ·Pages 584-95

Denver DR, Morris K, Kewalramani A, Harris KE, Chow A, Estes S, Lynch M, Thomas WK

Abstract

Homopolymeric nucleotide runs, also called mononucleotide microsatellites, are a ubiquitous, dominant, and mutagenic feature of eukaryotic genomes. A clear understanding of the forces that shape patterns of homopolymer evolution, however, is lacking. We provide a focused investigation of the abundance, chromosomal distribution, and mutation spectra of the four strand-specific homopolymer types (A, T, G, C) >or=8 bp in the genome of Caenorhabditis elegans. A and T homopolymers vastly outnumber G and C HPs, and the run-length distributions of A and T homopolymers differ significantly from G and C homopolymers. A scanning window analysis of homopolymer chromosomal distribution reveals distinct clusters of homopolymer density in autosome arms that are regions of high recombination in C. elegans. Dramatic biases are detected among closely spaced homopolymers; for instance, we observe 994 A homopolymers immediately followed by a T homopolymer (5' to 3') and only 8 instances of T homopolymers directly followed by an A homopolymer. Empirical homopolymer mutation assays in a set of C. elegans mutation-accumulation lines reveal an approximately 20-fold higher mutation rate for G and C homopolymers compared to A and T homopolymers. Nuclear A and T homopolymers are also found to mutate approximately 100-fold more slowly than mitochondrial A and T homopolymers. This integrative approach yields a total nuclear genome-wide homopolymer mutation rate estimate of approximately 1.6 mutations per genome per generation.

MeSH Terms
Animals Base Sequence Caenorhabditis elegans/genetics DNA Mutational Analysis Evolution, Molecular Genome Microsatellite Repeats/genetics Molecular Sequence Data Mutation/genetics Recombination, Genetic/genetics
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Denver Dee R
Department of Biology, Indiana University, 327 Jordan Hall, 1001 East Third Street, 47405, Bloomington, IN, USA. ddenver@bio.indiana.edu
Morris Krystalynne
Kewalramani Avinash
Harris Katherine E
Chow Amy
Estes Suzanne
Lynch Michael
Thomas W Kelley
References (44)
44 references, click to expand
  1. High direct estimate of the mutation rate in the mitochondrial genome of Caenorhabditis elegans.
    Science. 2000 Sep 29;289(5488):2342-4 PMID: 11009418
  2. The fitness effects of spontaneous mutations in Caenorhabditis elegans.
    Evolution. 2000 Aug;54(4):1234-46 PMID: 11005291
  3. Equilibrium distributions of microsatellite repeat length resulting from a balance between slippage events and point mutations.
    Proc Natl Acad Sci U S A. 1998 Sep 1;95(18):10774-8 PMID: 9724780
  4. Instability at sequence repeats in melanocytic tumours.
    Melanoma Res. 2001 Jun;11(3):283-9 PMID: 11468517
  5. Evolutionary origin, diversification and specialization of eukaryotic MutS homolog mismatch repair proteins.
    Nucleic Acids Res. 2000 Jan 15;28(2):463-71 PMID: 10606644
  6. Sequence composition and context effects on the generation and repair of frameshift intermediates in mononucleotide runs in Saccharomyces cerevisiae.
    Genetics. 2000 Oct;156(2):571-8 PMID: 11014807
  7. Microsatellites in the eukaryotic DNA mismatch repair genes as modulators of evolutionary mutation rate.
    Genome Res. 2001 Jul;11(7):1145-6 PMID: 11435395
  8. Distribution and abundance of microsatellites in the yeast genome can Be explained by a balance between slippage events and point mutations.
    Mol Biol Evol. 2000 Aug;17(8):1210-9 PMID: 10908641
  9. Exonucleolytic proofreading during replication of repetitive DNA.
    Biochemistry. 1996 Jan 23;35(3):1046-53 PMID: 8547240
  10. A bifurcated hydrogen-bonded conformation in the d(A.T) base pairs of the DNA dodecamer d(CGCAAATTTGCG) and its complex with distamycin.
    Proc Natl Acad Sci U S A. 1987 Dec;84(23):8385-9 PMID: 3479798
  11. Cryptic simplicity in DNA is a major source of genetic variation.
    Nature. 1986 Aug 14-20;322(6080):652-6 PMID: 3748144
  12. Yeast ARMs (DNA at-risk motifs) can reveal sources of genome instability.
    Mutat Res. 1998 May 25;400(1-2):45-58 PMID: 9685581
  13. Mobile elements and the genesis of microsatellites in dipterans.
    Mol Biol Evol. 2001 Mar;18(3):384-92 PMID: 11230539
  14. The structure of an oligo(dA).oligo(dT) tract and its biological implications.
    Nature. 1987 Nov 19-25;330(6145):221-6 PMID: 3670410
  15. Genome sequence of the nematode C. elegans: a platform for investigating biology.
    Science. 1998 Dec 11;282(5396):2012-8 PMID: 9851916
  16. Transposons but not retrotransposons are located preferentially in regions of high recombination rate in Caenorhabditis elegans.
    Genetics. 2000 Dec;156(4):1661-9 PMID: 11102365
  17. Natural variation and copulatory plug formation in Caenorhabditis elegans.
    Genetics. 1997 May;146(1):149-64 PMID: 9136008
  18. An extensive class of small RNAs in Caenorhabditis elegans.
    Science. 2001 Oct 26;294(5543):862-4 PMID: 11679672
  19. Evolution of repeated DNA sequences by unequal crossover.
    Science. 1976 Feb 13;191(4227):528-35 PMID: 1251186
  20. Frameshift mutations at coding mononucleotide repeat microsatellites in endometrial carcinoma with microsatellite instability.
    Cancer. 2000 May 15;88(10):2290-7 PMID: 10820351
  21. Microsatellite spreading in the human genome: evolutionary mechanisms and structural implications.
    Proc Natl Acad Sci U S A. 1996 Jun 25;93(13):6470-5 PMID: 8692839
  22. Phylogenetics in Caenorhabditis elegans: an analysis of divergence and outcrossing.
    Mol Biol Evol. 2003 Mar;20(3):393-400 PMID: 12644560
  23. Differential distribution of simple sequence repeats in eukaryotic genome sequences.
    Mol Biol Evol. 2001 Jul;18(7):1161-7 PMID: 11420357
  24. Short mononucleotide repeat sequence variability in mismatch repair-deficient cancers.
    Cancer Res. 2001 May 1;61(9):3801-5 PMID: 11325855
  25. High-throughput plasmid purification for capillary sequencing.
    Genome Res. 2001 Jul;11(7):1269-74 PMID: 11435410
  26. Fidelity of replication of repetitive DNA in mutS and repair proficient Escherichia coli.
    Mutat Res. 2001 Mar 1;474(1-2):1-14 PMID: 11239958
  27. Poly(dA:dT), a ubiquitous promoter element that stimulates transcription via its intrinsic DNA structure.
    EMBO J. 1995 Jun 1;14(11):2570-9 PMID: 7781610
  28. Recombinational and mutational hotspots within the human lipoprotein lipase gene.
    Am J Hum Genet. 2000 Jan;66(1):69-83 PMID: 10631137
  29. Microsatellite instability in yeast: dependence on the length of the microsatellite.
    Genetics. 1997 Jul;146(3):769-79 PMID: 9215886
  30. Simple sequence repeats as a source of quantitative genetic variation.
    Trends Genet. 1997 Feb;13(2):74-8 PMID: 9055609
  31. Distinct frequency-distributions of homopolymeric DNA tracts in different genomes.
    Nucleic Acids Res. 1998 Sep 1;26(17):4056-62 PMID: 9705519
  32. The contribution of slippage-like processes to genome evolution.
    J Mol Evol. 1995 Dec;41(6):1038-47 PMID: 8587102
  33. Microsatellite evolution: polarity of substitutions within repeats and neutrality of flanking sequences.
    Proc Biol Sci. 1999 Apr 22;266(1421):825-33 PMID: 10343406
  34. The rate of spontaneous mutation for life-history traits in Caenorhabditis elegans.
    Genetics. 1999 Jan;151(1):119-29 PMID: 9872953
  35. Genome-scale compositional comparisons in eukaryotes.
    Genome Res. 2001 Apr;11(4):540-6 PMID: 11282969
  36. Mini- and microsatellite expansions: the recombination connection.
    EMBO Rep. 2000 Aug;1(2):122-6 PMID: 11265750
  37. Meiotic recombination, noncoding DNA and genomic organization in Caenorhabditis elegans.
    Genetics. 1995 Sep;141(1):159-79 PMID: 8536965
  38. Selection against frameshift mutations limits microsatellite expansion in coding DNA.
    Genome Res. 2000 Jan;10(1):72-80 PMID: 10645952
  39. Base composition of mononucleotide runs affects DNA polymerase slippage and removal of frameshift intermediates by mismatch repair in Saccharomyces cerevisiae.
    Mol Cell Biol. 2002 Dec;22(24):8756-62 PMID: 12446792
  40. Hypermutability of homonucleotide runs in mismatch repair and DNA polymerase proofreading yeast mutants.
    Mol Cell Biol. 1997 May;17(5):2859-65 PMID: 9111358
  41. Formation of parallel four-stranded complexes by guanine-rich motifs in DNA and its implications for meiosis.
    Nature. 1988 Jul 28;334(6180):364-6 PMID: 3393228
  42. YPD, PombePD and WormPD: model organism volumes of the BioKnowledge library, an integrated resource for protein information.
    Nucleic Acids Res. 2001 Jan 1;29(1):75-9 PMID: 11125054
  43. Microsatellites in different eukaryotic genomes: survey and analysis.
    Genome Res. 2000 Jul;10(7):967-81 PMID: 10899146
  44. Polypurine/polypyrimidine sequences as cis-acting transcriptional regulators.
    Gene. 1997 Apr 29;190(1):17-26 PMID: 9185844
Article Info
Journal
Journal of molecular evolution
Abbr.
J Mol Evol
ISSN
0022-2844
DOI
10.1007/s00239-004-2580-4
Email
ddenver@bio.indiana.edu
Published
2004-05-00
Pages
584-95
Language
English
Region
Germany
NLM ID
0360051
Subset
IM
Grants
NIGMS NIH HHS · R01 GM-36827 · United States
Databases
GENBANK
AY219759, AY219760, AY219761, AY219762, AY219763, AY219764, AY219765, AY219766, AY219767, AY219768, AY219769, AY219770, AY219771, AY219772, AY219773, AY219774, AY219775, AY219776, AY219777, AY219778, AY219779, AY219780, AY219781, AY219782, AY219783, AY219784, AY219785, AY219786, AY219787, AY219788, AY219789
External Links
PubMed source DOI: 10.1007/s00239-004-2580-4 View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2